TY - INPR A1 - Hocher, Berthold A1 - Reichetzeder, Christoph T1 - Vitamin D and cardiovascular risk in postmenopausal women how to translate preclinical evidence into benefit for patients T2 - Kidney international : official journal of the International Society of Nephrology N2 - Preclinical work indicates that calcitriol restores vascular function by normalizing the endothelial expression of cyclooxygenase-2 and thromboxane-prostanoid receptors in conditions of estrogen deficiency and thus prevents the thromboxane-prostanoid receptor activation-induced inhibition of nitric oxide synthase. Since endothelial dysfunction is a key factor in the pathogenesis of cardiovascular diseases, this finding may have an important translational impact. It provides a clear rationale to use endothelial function in clinical trials aiming to find the optimal dose of vitamin D for the prevention of cardiovascular events in postmenopausal women. Y1 - 2013 U6 - https://doi.org/10.1038/ki.2013.139 SN - 0085-2538 VL - 84 IS - 1 SP - 9 EP - 11 PB - Nature Publ. Group CY - New York ER - TY - JOUR A1 - Hocher, Berthold A1 - Reichetzeder, Christoph A1 - Alter, Markus L. T1 - Renal and cardiac effects of DPP-4 inhibitors - from preclinical development to clinical research JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined Phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal Phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials - beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure. KW - DDP-4 inhibition KW - Diabetes KW - GLP-1 KW - Cardiovascular effects KW - Myocardial infarction KW - Kidney KW - Diabetic nephropathy KW - Acute renal failure Y1 - 2012 U6 - https://doi.org/10.1159/000339028 SN - 1420-4096 VL - 36 IS - 1 SP - 65 EP - 84 PB - Karger CY - Basel ER - TY - GEN A1 - Hocher, Berthold A1 - Reichetzeder, Christoph A1 - Dwi Putra, Sulistyo Emantoko A1 - Slowinski, Torsten A1 - Neuber, Corinna A1 - Kleuser, Burkhard A1 - Pfab, Thiemo T1 - Increased global placental DNA methylation levels are associated with gestational diabetes N2 - Background: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. It is known that GDM is associated with an altered placental function and changes in placental gene regulation. More recent studies demonstrated an involvement of epigenetic mechanisms. So far, the focus regarding placental epigenetic changes in GDM was set on gene-specific DNA methylation analyses. Studies that robustly investigated placental global DNA methylation are lacking. However, several studies showed that tissue-specific alterations in global DNA methylation are independently associated with type 2 diabetes. Thus, the aim of this study was to characterize global placental DNA methylation by robustly measuring placental DNA 5-methylcytosine (5mC) content and to examine whether differences in placental global DNA methylation are associated with GDM. Methods: Global DNA methylation was quantified by the current gold standard method, LC-MS/MS. In total, 1030 placental samples were analyzed in this single-center birth cohort study. Results: Mothers with GDM displayed a significantly increased global placental DNA methylation (3.22 ± 0.63 vs. 3.00 ± 0.46 %; p = 0.013; ±SD). Bivariate logistic regression showed a highly significant positive correlation between global placental DNA methylation and the presence of GDM (p = 0.0009). Quintile stratification according to placental DNA 5mC levels revealed that the frequency of GDM was evenly distributed in quintiles 1–4 (2.9–5.3 %), whereas the frequency in the fifth quintile was significantly higher (10.7 %; p = 0.003). Bivariate logistic models adjusted for maternal age, BMI, ethnicity, recurrent miscarriages, and familiar diabetes predisposition clearly demonstrated an independent association between global placental DNA hypermethylation and GDM. Furthermore, an ANCOVA model considering known predictors of DNA methylation substantiated an independent association between GDM and placental DNA methylation. Conclusions: This is the first study that employed a robust quantitative assessment of placental global DNA methylation in over a thousand placental samples. The study provides large scale evidence that placental global DNA hypermethylation is associated with GDM, independent of established risk factors. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 370 KW - Placenta KW - Gestational diabetes KW - Insulin resistance KW - LC-MS/MS KW - Global DNA methylation KW - Epigenetics KW - Hypermethylation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-400914 ER - TY - CHAP A1 - Hocher, Berthold A1 - Reichetzeder, Christoph A1 - von Websky, Karoline A1 - Tsuprykov, Oleg A1 - Klein, T. T1 - Dipeptidyl peptidase-4 inhibition in a rat model of ischaemia-reperfusion injury may accelerate tubular regeneration but does not improve glomerular filtration rate T2 - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) Y1 - 2014 SN - 0012-186X SN - 1432-0428 VL - 57 SP - S538 EP - S538 PB - Springer CY - New York ER - TY - CHAP A1 - Hocher, Berthold A1 - Tsuprykov, Oleg A1 - Alter, Markus L. A1 - von Websky, Karoline A1 - Chaykovska, Lyubov A1 - Antonenko, V. A1 - Rahnenführer, Jan A1 - Klein, T. A1 - Reichetzeder, Christoph T1 - Linagliptin and the angiotensin II receptor blocker telmisartan show comparable efficacy but different renoprotective pathways in rats with 5/6 nephrectomy T2 - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) Y1 - 2013 SN - 0012-186X SN - 1432-0428 VL - 56 IS - 15-16 SP - S66 EP - S66 PB - Springer CY - New York ER - TY - JOUR A1 - Li, Jian A1 - Lu, Yong Ping A1 - Reichetzeder, Christoph A1 - Kalk, Philipp A1 - Kleuser, Burkhard A1 - Adamski, Jerzy A1 - Hocher, Berthold T1 - Maternal PCaaC38:6 is Associated With Preterm Birth - a Risk Factor for Early and Late Adverse Outcome of the Offspring JF - Journal of European public policy N2 - Background/Aims: Preterm birth (PTB) and low birth weight (LBW) significantly influence mortality and morbidity of the offspring in early life and also have long-term consequences in later life. A better understanding of the molecular mechanisms of preterm birth could provide new insights regarding putative preventive strategies. Metabolomics provides a powerful analytic tool to readout complex interactions between genetics, environment and health and may serve to identify relevant biomarkers. In this study, the association between 163 targeted maternal blood metabolites and gestational age was investigated in order to find candidate biomarkers for PTB. Methods: Five hundred twenty-three women were included into this observational study. Maternal blood was obtained before delivery. The concentration of 163 maternal serum metabolites was measured by flow injection tandem mass spectrometry. To find putative biomarkers for preterm birth, a three-step analysis was designed: bivariate correlation analysis followed by multivariable regression analysis and a comparison of mean values among gestational age groups. Results: Bivariate correlation analysis showed that 2 acylcarnitines (C16:2, C2), 1 amino acids (xLeu), 8 diacyl-PCs (PCaaC36:4, PCaaC38:4, PCaaC38:5, PCaaC38:6, PCaaC40:4, PCaaC40:5, PCaaC40:6, PCaaC42:4), and 1 Acylalkyl-PCs (PCaeC40:5) were inversely correlated with gestational age. Multivariable regression analysis confounded for PTB history, maternal body mass index (BMI) before pregnancy, systolic blood pressure at the third trimester, and maternal body weight at the third trimester, showed that the diacyl-PC PCaaC38:6 was the only metabolite inversely correlated with gestational age. Conclusions: Maternal blood concentrations of PCaaC38:6 are independently associated with gestational age. (C) 2016 The Author(s) Published by S. Karger AG, Basel KW - Metabolomics KW - PCaaC38:6 KW - Biomarker KW - Preterm birth Y1 - 2016 U6 - https://doi.org/10.1159/000443428 SN - 1420-4096 SN - 1423-0143 VL - 41 SP - 250 EP - 257 PB - Karger CY - Basel ER - TY - JOUR A1 - Li, Jian A1 - Lu, Yong-Ping A1 - Tsuprykov, Oleg A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Reichetzeder, Christoph A1 - Tian, Mei A1 - Zhang, Xiao Li A1 - Zhang, Qin A1 - Sun, Guo-Ying A1 - Guo, Jingli A1 - Gaballa, Mohamed Mahmoud Salem Ahmed A1 - Peng, Xiao-Ning A1 - Lin, Ge A1 - Hocher, Berthold T1 - Folate treatment of pregnant rat dams abolishes metabolic effects in female offspring induced by a paternal pre-conception unhealthy diet JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Aims/hypothesis Paternal high-fat diet prior to mating programmes impaired glucose tolerance in female offspring. We examined whether the metabolic consequences in offspring could be abolished by folate treatment of either the male rats before mating or the corresponding female rats during pregnancy. Methods Male F0 rats were fed either control diet or high-fat, high-sucrose and high-salt diet (HFSSD), with or without folate, before mating. Male rats were mated with control-diet-fed dams. After mating, the F0 dams were fed control diet with or without folate during pregnancy. KW - Glucose tolerance KW - High-fat-sucrose-salt diet KW - Maternal folate treatment KW - Paternal programming Y1 - 2018 U6 - https://doi.org/10.1007/s00125-018-4635-x SN - 0012-186X SN - 1432-0428 VL - 61 IS - 8 SP - 1862 EP - 1876 PB - Springer CY - New York ER - TY - JOUR A1 - Li, Jian A1 - Shen, Jinhua A1 - Zhang, Xiaoli A1 - Peng, Yangqin A1 - Zhang, Qin A1 - Hu, Liang A1 - Reichetzeder, Christoph A1 - Zeng, Suimin A1 - Li, Jing A1 - Tian, Mei A1 - Gong, Fei A1 - Lin, Ge A1 - Hocher, Berthold T1 - Risk factors associated with preterm birth after IVF/ICSI JF - Scientific reports N2 - In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is associated with an increased risk of preterm (33rd-37th gestational week) and early preterm birth (20th-32nd gestational week). The underlying general and procedure related risk factors are not well understood so far. 4328 infertile women undergoing IVF/ICSI were entered into this study. The study population was divided into three groups: (a) early preterm birth group (n = 66), (b) preterm birth group (n = 675) and (c) full-term birth group (n = 3653). Odds for preterm birth were calculated by stepwise multivariate logistic regression analysis. We identified seven independent risk factors for preterm birth and four independent risk factors for early preterm birth. Older (> 39) or younger (< 25) maternal age (OR: 1.504, 95% CI 1.108-2.042, P = 0.009; OR: 2.125, 95% CI 1.049-4.304, P = 0.036, respectively), multiple pregnancy (OR: 9.780, 95% CI 8.014-11.935, P < 0.001; OR: 8.588, 95% CI 4.866-15.157, P < 0.001, respectively), placenta previa (OR: 14.954, 95% CI 8.053-27.767, P < 0.001; OR: 16.479, 95% CI 4.381-61.976, P < 0.001, respectively), and embryo reduction (OR: 3.547, 95% CI 1.736-7.249, P = 0.001; OR: 7.145, 95% CI 1.990-25.663, P = 0.003, respectively) were associated with preterm birth and early preterm birth, whereas gestational hypertension (OR: 2.494, 95% CI 1.770-3.514, P < 0.001), elevated triglycerides (OR: 1.120, 95% CI 1.011-1.240, P = 0.030) and shorter activated partial thromboplastin time (OR: 0.967, 95% CI 0.949-0.985, P < 0.001) were associated only with preterm birth. In conclusion, preterm and early preterm birth risk factors in patients undergoing assisted IVF/ICSI are in general similar to those in natural pregnancy. The lack of some associations in the early preterm group was most likely due to the lower number of early preterm birth cases. Only embryo reduction represents an IVF/ICSI specific risk factor. Y1 - 2022 U6 - https://doi.org/10.1038/s41598-022-12149-w SN - 2045-2322 VL - 12 IS - 1 PB - Nature Research CY - Berlin ER - TY - JOUR A1 - Li, Jian A1 - Wang, Zi-Neng A1 - Chen, You-Peng A1 - Dong, Yun-Peng A1 - Shuai, Han-Lin A1 - Xiao, Xiao-Min A1 - Reichetzeder, Christoph A1 - Hocher, Berthold T1 - Late gestational maternal serum cortisol is inversely associated with fetal brain growth JF - Neuroscience & biobehavioral reviews : official journal of the International Behavioral Neuroscience Society N2 - To analyze the association between fetal brain growth and late gestational blood serum cortisol in normal pregnancy.Blood total cortisol was quantified at delivery in 432 Chinese mother/child pairs. Key inclusion criteria of the cohort were: no structural anomalies of the newborn, singleton pregnancy, no alcohol abuse, no drug abuse or history of smoking no hypertensive disorders and no impairment of glucose tolerance and no use of steroid medication during pregnancy. Differential ultrasound examination of the fetal body was done in early (gestational day 89.95 +/- 7.31), middle (gestational day 160.17 16.12) and late pregnancy (gestational day 268.89 +/- 12.42). Newborn's cortisol was not correlated with any of the ultrasound measurements during pregnancy nor with birth weight. Multivariable regression analysis, considering timing of the ultrasound examination, the child's sex, maternal BMI, maternal age, maternal body weight at delivery, the timing of cortisol measurement and maternal uterine contraction states, revealed that maternal serum total cortisol was significantly negative correlated with ultrasound parameters describing the fetal brain: late biparietal diameter (R-2 =0.512, p =0.009), late head circumference (R-2 = 0.498, p= 0.001), middle biparietal diameter (R-2= 0.819, p = 0.013), middle cerebellum transverse diameter R-2 = 0.76, p= 0.014) and early biparietal diameter(R-2 = 0.819, p = 0.013). The same analysis revealed that birth weight as well as ultrasound parameters such as abdominal circumference and femur length were not correlated to maternal cortisol levels. In conclusion, our study demonstrates that maternal cortisol secretion within physiological ranges may be inversely correlated to fetal brain growth but not to birth weight. It remains to be demonstrated whether maternal cortisol secretion negatively influencing fetal brain growth translates to adverse neurological outcomes in later life. KW - Brain development KW - Fetal programming KW - Cortisol Maternal cortisol KW - Head circumference KW - Biparietal diameter Y1 - 2012 U6 - https://doi.org/10.1016/j.neubiorev.2011.12.006 SN - 0149-7634 VL - 36 IS - 3 SP - 1085 EP - 1092 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Lu, Yong-Ping A1 - Reichetzeder, Christoph A1 - Prehn, Cornelia A1 - von Websky, Karoline A1 - Slowinski, Torsten A1 - Chen, You-Peng A1 - Yin, Liang-Hong A1 - Kleuser, Burkhard A1 - Yang, Xue-Song A1 - Adamski, Jerzy A1 - Hocher, Berthold T1 - Fetal serum metabolites are independently associated with Gestational diabetes mellitus JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM. (c) 2018 The Author(s) Published by S. Karger AG, Basel KW - Gestational diabetes KW - Metabolomics KW - Phosphatidylcholine acyl-alkyl C 32:1 KW - Proline Y1 - 2018 U6 - https://doi.org/10.1159/000487119 SN - 1015-8987 SN - 1421-9778 VL - 45 IS - 2 SP - 625 EP - 638 PB - Karger CY - Basel ER -